BACKGROUND: L-arginine is the precursor of endothelium-derived nitric oxide, an endogenous vasodilator. L-arginine supplementation improves vascular reactivity and functional capacity in peripheral arterial disease (PAD) in small, short-term studies. We aimed to determine the effects of long-term administration of L-arginine on vascular reactivity and functional capacity in patients with PAD. METHODS AND RESULTS: The Nitric Oxide in Peripheral Arterial Insufficiency (NO-PAIN) study was a randomized clinical trial of oral L-arginine (3 g/d) versus placebo for 6 months in 133 subjects with intermittent claudication due to PAD in a single-center setting. The primary end point was the change at 6 months in the absolute claudication distance as assessed by the Skinner-Gardner treadmill protocol. L-arginine supplementation significantly increased plasma L-arginine levels. However, measures of nitric oxide availability (including flow-mediated vasodilation, vascular compliance, plasma and urinary nitrogen oxides, and plasma citrulline formation) were reduced or not improved compared with placebo. Although absolute claudication distance improved in both L-arginine- and placebo-treated patients, the improvement in the L-arginine-treated group was significantly less than that in the placebo group (28.3% versus 11.5%; P=0.024). CONCLUSIONS: In patients with PAD, long-term administration of L-arginine does not increase nitric oxide synthesis or improve vascular reactivity. Furthermore, the expected placebo effect observed in studies of functional capacity was attenuated in the L-arginine-treated group. As opposed to its short-term administration, long-term administration of L-arginine is not useful in patients with intermittent claudication and PAD.

in before the sh*t storm.

no but seriously...this thread is for discussion. not for pimping ANY products. if you'd like to discuss the science of arginine, please join in.

I will admit defeat on that issue. I spoke too soon it seems as during short term supplementation of arginine, it will not increase, however upon long term it will.

The main thing to grasp from this though is this:

However, measures of nitric oxide availability (including flow-mediated vasodilation, vascular compliance, plasma and urinary nitrogen oxides, and plasma citrulline formation) were reduced or not improved compared with placebo. Although absolute claudication distance improved in both L-arginine- and placebo-treated patients, the improvement in the L-arginine-treated group was significantly less than that in the placebo group (28.3% versus 11.5%; P=0.024). CONCLUSIONS: In patients with PAD, long-term administration of L-arginine does not increase nitric oxide synthesis or improve vascular reactivity.

I will admit defeat on that issue. I spoke too soon it seems as during short term supplementation of arginine, it will not increase, however upon long term it will.

The main thing to grasp from this though is this:

teres a good explanation for why arg stops werking, wuz by gaspari, on there plasmajet. They compare the likeness of nitro heart pills to the NO produced by arg. they go on to say that to keep the pumps from the NO that you need to supplement extremely high doses of C to keep the body producing NO from arg. I have yet to see any research studied or abstracts on this, so it may just be a sales line.

also taking on an empty stomache also has sumthing to do with the equation also.

Increased production of free radicals under oxidative stress conditions plays a vital role in the impairment of endothelial function and also in the pathogenesis of ischemic heart diseases. Ischemia, followed by reperfusion, leads to the exacerbated formation of oxy- free radicals. These reactive oxygen species through a chain of reactions damage the cardiomyocytes and cause more injury to the myocardium. L-Arginine is reported to act as free radical scavenger, inhibits the activity of pro-oxidant enzymes and thus acts as an antioxidant and these roles of L-arginine are mediated by nitric oxide (NO). In the present study, the effect of oral administration of L-arginine (3 g/day for 7 days) on some antioxidant enzymes, total thiols, lipid peroxidation measured as malondialdehyde (MDA), and plasma ascorbate levels in myocardial ischemic patients was investigated. We observed an increase in the activity of superoxide dismutase (SOD), total thiols (T-SH) and plasma ascorbate levels and a decrease in the activity of xanthine oxidase (XO), MDA levels, carbonyl content and serum cholesterol in the patients on oral administration of L-arginine. The present study demonstrates that L-arginine administration may be beneficial to patients with myocardial ischemic disorders, such as acute myocardial infarction and acute angina.

BACKGROUND: Several lines of evidence point to the dysfunction of the endothelial l-arginine-NO system in preeclampsia. We investigated the influence of dietary supplementation with l-arginine on blood pressure and biochemical measures of NO production in women with preeclampsia in prospective, randomized, placebo-controlled study. DESIGN: The 61 preeclamptic women on a standardized low nitrate diet received orally 3 g of l-arginine (n = 30) or placebo (n = 31) daily for 3 weeks as a supplement to standard therapy. The differences between the two groups in systolic (SBP), diastolic (DBP) and mean arterial blood pressures (MAP) as well as in plasma levels of selected aminoacids, plasma concentrations of nitrates/nitrites (NOx) and in 24-h urine NOx excretion were determined. RESULTS: After 3 weeks of treatment, values of SBP, DPB and MAP were significantly lower in the group taking l-arginine as compared with the placebo group (SBP: 134.2 +/- 2.9 vs. 143.1 +/- 2.8; DBP: 81.6 +/- 1.7 vs. 86.5 +/- 0.9; MAP: 101.8 +/- 1.5 vs. 108.0 +/- 1.2 mmHg, P < 0.01). Importantly, treatment with exogenous l-arginine significantly elevated 24-h urinary excretion of NOx and mean plasma levels of l-citrulline. Exogenous l-arginine did not influence plasma concentrations of l-arginine, l-ornithine and methylated arginines (ADMA, SDMA, L-NMMA). CONCLUSIONS: We conclude that in women with preeclampsia, prolonged dietary supplementation with l-arginine significantly decreased blood pressure through increased endothelial synthesis and/or bioavailability of NO. It is tempting to speculate that the supplementary treatment with l-arginine may represent a new, safe and efficient strategy to improve the function of the endothelium in preeclampsia.

Med Sci Monit. 2004 Jan;10(1):CR29-32.
The influence of two different doses of L-arginine oral supplementation on nitric oxide (NO) concentration and total antioxidant status (TAS) in atherosclerotic patients.

BACKGROUND: The purpose of this study was to assess the effect of two different doses in 28-day L-arginine oral supplementation on nitric oxide (NO) concentration and total antioxidant status (TAS) in patients with atherosclerotic peripheral arterial disease at Fontaine's stages II and III. MATERIAL/METHODS: 32 patients were divided into 2 groups receiving L-arginine at 3i2 g/day (group A) or 3i4 g/day (group B). Nitric oxide concentration was determined with the testing set provided by Oxis using a Hyperion Micro Reader. Total antioxidant status (TAS) in mmol/l was established in serum with the RANDOX NX2332 test. RESULTS: Group A showed substantially higher NO levels after 14 and 28 days of therapy. In group B, the NO level increase was substantial after 28 days. Noticeably higher total antioxidant statuses were noted in both groups: group A showed this only after 28 days of treatment, while group B exhibited substantial increase in TAS after 7, 14 and 28 days of L-arginine supplementation. CONCLUSIONS: Oral supplementation of L-arginine for 28 days leads to substantial increases in NO and TAS levels (comparable in both groups of patients) in the blood of patients with atherosclerotic peripheral arterial disease at Fontaine's stages II and III. The TAS concentration rise points to an antioxidative effect of L-arginine oral supplementation.

OBJECTIVES: Arginine is converted in the endothelial cells to nitric oxide (NO) and citrulline. NO is a potent vasodilator in humans, but diabetics may have a reduced generation of NO which results in endothelial dysfunction. The aim of this study was to evaluate the effects of oral arginine on nitric oxide production, counter-regulatory hormones and blood pressure in mildly hypertensive type 2 diabetic patients. METHODS: A prospective, crossover clinical trial was performed over a three-day stay in the General Clinical Research Center. Six patients with type 2 diabetes mellitus and mild hypertension consented and were given orally three grams of arginine per hour for 10 hours on either day 2 or day 3. On both days 2 and 3, blood pressure was monitored between 5 AM and 4 PM and mean pressure determined. RESULTS: Oral arginine increased plasma citrulline from 31.3 +/- 6.0 to 41.5 +/- 6.0 micro mol/L (mean +/- SEM; p < 0.05) which may reflect an increased conversion of arginine into NO and citrulline. Arginine reduced systolic BP from 135 +/- 7 to 123 +/- 8 mmHg; p < 0.05. Diastolic BP fell from 86.9 +/- 1.7 to 80.7 +/- 2.4 mmHg; p < 0.05). The reduction in BP was noted to occur two hours after starting oral arginine, and BP returned to normal within one hour of stopping the arginine. The oral arginine had no effect on C-peptide, insulin or other hormone concentrations. CONCLUSIONS: These data suggest that oral arginine may increase endothelial nitric oxide synthase (NOS) to increase vascular NO and temporally reduce blood pressure in mildly hypertensive type 2 diabetic patients.

Bottom line, there is conflicting data from studies. In healthy trained individuals, oral arginine increases pumps, as demonstrated by hundreds of thousands of users over ten years.

BACKGROUND: L-arginine is the precursor of endothelium-derived nitric oxide, an endogenous vasodilator. L-arginine supplementation improves vascular reactivity and functional capacity in peripheral arterial disease (PAD) in small, short-term studies. We aimed to determine the effects of long-term administration of L-arginine on vascular reactivity and functional capacity in patients with PAD. METHODS AND RESULTS: The Nitric Oxide in Peripheral Arterial Insufficiency (NO-PAIN) study was a randomized clinical trial of oral L-arginine (3 g/d) versus placebo for 6 months in 133 subjects with intermittent claudication due to PAD in a single-center setting. The primary end point was the change at 6 months in the absolute claudication distance as assessed by the Skinner-Gardner treadmill protocol. L-arginine supplementation significantly increased plasma L-arginine levels. However, measures of nitric oxide availability (including flow-mediated vasodilation, vascular compliance, plasma and urinary nitrogen oxides, and plasma citrulline formation) were reduced or not improved compared with placebo. Although absolute claudication distance improved in both L-arginine- and placebo-treated patients, the improvement in the L-arginine-treated group was significantly less than that in the placebo group (28.3% versus 11.5%; P=0.024). CONCLUSIONS: In patients with PAD, long-term administration of L-arginine does not increase nitric oxide synthesis or improve vascular reactivity. Furthermore, the expected placebo effect observed in studies of functional capacity was attenuated in the L-arginine-treated group. As opposed to its short-term administration, long-term administration of L-arginine is not useful in patients with intermittent claudication and PAD. .

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The problem with this study is that it is done on subjects that suffer from PAD. Nitric-oxide from L-Arginine is endothelium derived.

Now, follow me here. Peripheral Arterial Disease (PAD) occurs when arteries that supply blood to the arms, legs, and groin become blocked (caused by Atherosclerosis). Every single person with atherosclerosis has ENDOTHELIAL DYSFUNCTION. Hence, the issue here.

no but seriously...this thread is for discussion. not for pimping ANY products. if you'd like to discuss the science of arginine, please join in.

What happened to the discussion? I provided feedback on the study you posted, as to why it was unapplicable. Do you understand the point I made? I would like to hear if you agree and concede on this specific point, or if you have another angle. You know, a discussion and all that.

I kind of got the feelling that you started that thread to eventually pump up Hemavol, which some people didn't like.

I will admit that that product looks awsome.

My comment on arginine is that a "NO PAIN" study won't cut it for me. I whant to see a study done on some top level natural bodybuilders, specifically during training.

They're a vendor here, they SHOULD PIMP. The problem I had was that what they were saying was plain wrong, and in saying it, they were going against proven research, AND unequivocal user feedback. When you say the opposite of research and, oh, 50 gazzillion servings of arginine used by 50 bazziollion happy, impressed users, you should expect at best, to be questioned, at worst, ridiculed.

I'm tempted to start a thread on agmantine, but it's been covered here. Strategic has posted beefy studies on it, as has dinoii. I'm still not impressed.

regardless of what u think of arginine......there are studies that show it increases performance in healthy trained individuals....so even if it didnt increase NO.....it would still be a legit product to use.....first study i can think of was a gnc study to determine dosage on the Maxertion NO product

What happened to the discussion? I provided feedback on the study you posted, as to why it was unapplicable. Do you understand the point I made? I would like to hear if you agree and concede on this specific point, or if you have another angle. You know, a discussion and all that.

The information is geared towards patients with PAD; however, I don't think that means this has zero bearing for sports nutrition. After all, we all have the same metabolic reactions in our bodies, some just go at different rates.

There have been many papers written about arginine for short term use. This paper investigating long-term use appears to show otherwise.

From what I've gathered, a major cause is linked to the formation of ADMA, which seems to deter production of NO. Provided this is the case, we've got ourselves into parallel enzymatic reactions. I don't know the half life of ADMA, but from a quick look at its structure, I can tell you that NO isn't going to be in the same order of magnitude.

Provided the previous data, suggesting short term supplementation is effective and assuming that all other parameters are not significantly changing (i.e. concentration of enzymes, methyl-donors, etc.) this enables us to conclude that the rate NO production is more readily enhanced with increased arginine concentration than that of ADMA. Please note, however, that rates of both reactions will be increased through increased arginine levels.

Going back to my previous statement about half-lives, I'm hoping by this point in my post that it seems quite logical that ADMA levels will continue to build up and therefore hinder NO production.

That being siad, I really don't think its going to be out of the way to say that arginine supplementation may be better if cycled.

The information is geared towards patients with PAD; however, I don't think that means this has zero bearing for sports nutrition. After all, we all have the same metabolic reactions in our bodies, some just go at different rates.

Actually it is huge. Again, Arginine is the source of Endothelium-derived NO. Yet, PAD patients(the subjects of the study) have severe endothelial dysfunctions that impair their ability to produce NO in the first place.

It is like stating 'product-x' failed to increase RBC counts in terminal bone marrow cancer patients or that wasting diease patients given bcaa's failed to gain muscle mass. It is flawed from the inception, thus irrelevant.

Before using this study it any context, I would implore anyone to first research PAD as well as Atherosclerosis.

I've never seen an arginine product recommend NOT cycling. Either people use it pre-workout only, which should greatly prevent any negative associated with long term use, or they use it for a straight for month or three, then take some time off.